Systems and methods for improved visualization during minimally invasive procedures

ABSTRACT

Systems and methods are provided for performing a minimally invasive procedure in an automated or semi-automated fashion, where an imaging probe having an imaging modality compatible with the presence of an intraluminal medium is employed to record images that are processed to identify regions of interest and direct a medium displacement operation during a subsequent minimally invasive operation that benefits from the displacement of the intraluminal medium. The minimally invasive operation may include recording images with a second imaging modality, or may be a therapeutic treatment. The method is may be performed in real-time, where images obtained from the first imaging modality are processed in real time to determine whether or not the minimally invasive operation is to be performed at a given position.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Application No.61/411,225, titled “SYSTEMS AND METHODS FOR IMPROVED VISUALIZATIONDURING MINIMALLY INVASIVE PROCEDURES” and filed on Nov. 8, 2010, theentire contents of which are incorporated herein by reference.

BACKGROUND

The present disclosure relates generally to the field of high resolutionmedical imaging. More particularly, the present disclosure relates tominimally invasive methods involving two or more imaging modalities.

High resolution medical imaging has broad diagnostic utility, includingassessing tissue structures, anatomy and/or composition, planning and/orguiding interventions on localized regions of the body, and assessingthe result of interventions that alter the structure, composition orother properties of the localized region. Among the many different highresolution imaging modalities, high frequency ultrasound and opticalcoherence tomography are two highly useful clinical and research tools.

High frequency ultrasound is a technique that is particularly useful forintravascular and intracardiac procedures. For these applications, oneor more ultrasound transducers are incorporated into a catheter or otherdevice that can be inserted into the body. Two particularly importantimplementations of high frequency ultrasound are intravascularultrasound (IVUS), for imaging blood vessels, and intracardiacechocardiography (ICE) for imaging cardiac chambers. Both ICE and IVUSare minimally invasive, and involve placing one or more ultrasoundtransducers inside a blood vessel or cardiac chamber to take highquality images of these structures.

The center frequency of IVUS typically lies within the range of 3 to 200MHz and more typically in the range of 8 to 80 MHz. Higher frequenciesprovide higher resolution but result in worse signal penetration andthus a smaller field of view. Depth of penetration can range from lessthan a millimeter to several centimeters depending on several parameterssuch as center frequency and geometry of the transducer, the attenuationof the media through which the imaging occurs andimplementation-specific specifications that affect the signal to noiseratio of the system.

High resolution imaging methods often involve the use of a rotary shaftto transmit torque to an imaging device near the distal end of theprobe. These rotary shafts are often long, thin and flexible so thatthey can be delivered through anatomical conduits, such as thevasculature, genitourinary tracts, respiratory tracts and other suchbodily lumens. Ideally, when torque is applied to the cable in aspecified direction the torque cable develops a property of having aclose relation between the degree of rotation at its proximal and distalends. This allows the simplification of the design of an ultrasoundcatheter by making the angle of rotation at the distal end of the torquecable (within the body) a reasonable approximation of the angle ofrotation at the proximal end of the torque cable (outside of the body).

Other imaging systems operate without a torque cable, such as angioscopycatheters (which employ fiber optic bundles) and phased array imagingsystems. Additionally, imaging systems have been proposed anddemonstrated that incorporate a micro-motor in the distal end of thecatheter instead of relying on a torque cable.

Variations of high frequency ultrasound exist, where the signalacquisition and/or analysis of the backscattered signal is modified tofacilitate obtaining or inferring further information about the imagedtissue. These include elastography, where the strain within tissue isassessed as the tissue is compressed at different blood pressures (deKorte et al Circulation. 2002 Apr. 9; 105(14):1627-30); Doppler imagingwhich assesses motion such as blood flow within anatomic structures;virtual histology, which attempts to infer the composition of tissueusing the radio-frequency properties of the backscattered signalcombined with a pattern recognition algorithm (Nair, U.S. Pat. No.6,200,268); second harmonic imaging (Goertz et al, Invest Radiol. 2006August; 41(8):631-8) and others. Ultrasound transducers are improvingconsiderably, including the use of single crystal ultrasound transducersand composite ultrasound transducers.

A catheter-based system for intravascular ultrasound is described byYock (U.S. Pat. No. 4,794,931) to provide high resolution imaging ofstructures in blood vessels. This system comprises an outer sheath,within which there is an ultrasound transducer near the distal end of along torque cable. When a motor rotates the torque cable and ultrasoundtransducer assembly, 2D cross-sectional images of anatomical structures,such as blood vessels, can be made. Linear translation of the catheteror the torque cable and ultrasound transducer in combination with therotational motion of the ultrasound transducer allows for acquisition ofa series of 2D images along the length of the catheter.

Hossack et al (WO/2006/121851) describe a forward looking ultrasoundtransducer using a CMUT transducer and a reflective surface.

Optical imaging methods based on fiber optic technology used in thefield of medicine include optical coherence tomography (OCT),angioscopy, near infrared spectroscopy, Raman spectroscopy andfluorescence spectroscopy. These modalities typically require the use ofone or more optical fibers to transmit light energy along a shaftbetween an imaging site and an imaging detector.

Optical coherence tomography is an optical analog of ultrasound, andprovides imaging resolutions on the order of 1 to 30 microns, but doesnot penetrate as deeply into tissue as ultrasound in most cases. Fiberoptics can also be used to deliver energy for therapeutic maneuvers suchas laser ablation of tissue and photodynamic therapy. Other usefuloptical imaging modalities include endoscopy and other similar orrelated imaging mechanisms that involve the use of a probe to obtainimages based on the back-reflection of light. Miniaturization ofdetectors and light sources is making it possible to include the lightsources and/or detectors in the catheter itself, potentially obviatingthe need for fiber optics to act as an intermediary component in thetransmission and/or detection of light.

Optical coherence tomography is limited by its small penetration depth(on the order of 500 to 3000 microns) in most biologic media. Most suchmedia, including blood, are not optically transparent. OCT has thus farrequired the displacement of blood to create an optically clearenvironment for this purpose. One approach is to displace the blood withanother fluid prior to performing measurements with the imaging modalityincompatible with blood. U.S. Pat. No. 7,625,366, issued to Atlas,provides an exemplary flush catheter for injecting a flush solution intoa vessel for performing OCT measurements with minimal blooddisplacement. Fluids that have been either used or contemplated for thispurpose include radio-opaque contrast or various formulations of saline,Ringer's lactate and others. U.S. Pat. No. 7,794,446 (issued to Bosse etal.) and U.S. Pat. No. 7,747,315 (issued to Villard et al.) discloseimproved flush solution compositions for use in OCT imaging.

Displacement of blood by the introduction of another fluid with greatertransparency provides a time interval in which optical coherencetomography imaging can occur. This time window can be extended byreducing the flow within the vessel, such as by the use guide cathetersthat incorporate an occlusion balloon. For example, U.S. Pat. Nos.5,722,403, 5,740,808, 5,752,158, 5,848,969, 5,904,651, and 6,047,218,issued to McGee et al., provide imaging catheter systems including aninflatable balloon that incorporates an imaging apparatus. U.S. Pat. No.7,674,240, issued to Webler et al., provides improved devices forinflating and deflating balloons for occluding a vessel.

Displacement of blood by means of introduction of another fluid toimprove OCT imaging is conventionally done by a manual process, wherethe operator injects the transparent fluid on one or more occasionsduring an imaging procedure. Such injection may be done via a number ofmethods, including use of a manual syringe, use of pressurized fluiddelivery systems and use of powered pumps. Pressurized fluid deliverysystems can include the simple use of gravitational forces to providepressure, as well as devices that apply pressure to a compressible ordeformable compartment filled with the fluid of interest. For example,pressure infuser bags use an inflatable bladder, similar to that of aconventional blood pressure cuff, to apply pressure to a bag of fluidwithin a confined compartment. The inflatable bladder and the bag offluid share a confined space. Therefore, when the bladder is inflated,such as with a manual hand pump, pressurized infusions of fluid into apatient is possible.

Alternatively, blood can be displaced by use of a balloon filled with anoptically clear medium, such as radio-opaque contrast, saline or air.The balloon may surround the region of the catheter where light, such asthat used for OCT imaging or near infra-red (NIR) spectroscopy, exitsthe imaging probe.

Unfortunately, complications can arise when displacing blood from avessel. For example, there is a small risk of embolic events, if theintroduction of displaced fluid dislodges particles from the vesselwall. There is a risk of causing or worsening a dissection between thelayers of the vessel wall if fluid is injected inadvertently with toomuch force, or if the fluid is injected near a pre-existing dissectionsite. In critical organs such as the heart, the potential complicationsof displacing blood with another fluid include ischemia to the targetorgan and arrhythmias. Cardiac arrhythmias may occur as a result ofhypoxia if the displacing fluid does not carry adequate oxygen to themyocardium. They may also occur due to changes in the concentrations ofelectrolytes in the myocardium.

For vessels that perfuse critical organs sensitive to hypoxia, such asthe heart, brain and kidneys, prolonged intervals of blood displacementand/or vascular occlusion can lead to adverse clinical events, and theoperator may be compelled to minimize the duration of time over whichthe displacement of blood occurs.

The need to minimize the amount of time during which blood is displacedhas to be balanced with the desire to acquire an adequate amount ofimaging data. For example, if the imaging probe is translated along thevessel's longitudinal axis, the portion of the vessel adequately imagedby an optical imaging technique will be limited by the length of timeduring which blood is displaced adequately. Not only is the timeduration over which blood is displaced of importance, but if aninjection of an optically transmissive fluid is being used, then thevolume of fluid injected may have important consequences.

For example, some operators use radio-opaque contrast as the opticallytransmissive medium. Yet it is well known in the field of medicine thatcontrast agents frequently have deleterious effects on kidney functionand can contribute to acute renal failure. Conversely, inadequatedisplacement of blood results in sub-optimal imaging.

Variations of optical coherence tomography (OCT) include polarizationsensitive OCT (PS-OCT) where the birefringent properties of tissuecomponents can be exploited to obtain additional information aboutstructure and composition; spectroscopic OCT which similarly providesimproved information regarding the composition of the imaged structures;Doppler OCT which provides information regarding flow and motion;elastography via OCT; and optical frequency domain imaging (OFDI), whichallows for a markedly more rapid acquisition of imaging data andtherefore enables imaging to occur over a larger volume of interest inless time.

There exist several other forms of fiber-optic based imaging other thanOCT. Amundson et al describe a system for imaging through blood usinginfrared light (U.S. Pat. No. 6,178,346). The range of theelectromagnetic spectrum that is used for their imaging system isselected to be one which optimizes penetration through blood, allowingoptical imaging through blood similar to that afforded by angioscopy inthe visible spectrum, but without the need to flush blood away from theregion being imaged.

Tearney et al (U.S. Pat. No. 6,134,003) describe several embodimentsthat enable optical coherence tomography to provide higher resolutionimaging than is readily obtained by high frequency ultrasound or IVUS.

Dewhurst (U.S. Pat. No. 5,718,231) discloses a forward looking probe forintravascular imaging where a fiber optic travels through an ultrasoundtransducer to shine light on a target tissue straight in front of theend of the probe. The light then interacts with the target tissue andmakes ultrasound waves, which are received by the ultrasound sensor andthe images are photoacoustic images only as the system is not configuredto receive and process optical images. The ultrasound sensor used in theDewhurst device is limited to thin film polymeric piezoelectrics, suchas thin film PVDF, and is used only to receive ultrasound energy, not toconvert electrical energy to ultrasound.

Angioscopy, endoscopy, bronchoscopy and many other imaging devices havebeen described which allow for the visualization of internal conduitsand structures (such as vessels, gastrointestinal lumens and thepulmonary system) in mammalian bodies based on the principle ofilluminating a region within the body near the distal end of a rigid orflexible shaft. Images are then created by either having a photodetectorarray (such as a CCD array) near the end of the shaft or by having abundle of fiber optics transmit the received light from the distal endof the shaft to the proximal end where a photodetector array or othersystem that allows the operator to generate or look at an imagerepresentative of the illuminated region. Fiber bundles are bulky andreduce the flexibility of the shaft among other disadvantages.

Other fiber optic based modalities for minimally invasive assessment ofanatomic structures include Raman spectroscopy as described by Motz etal. (J Biomed Opt. 2006 March-April; 11(2)), near infrared spectroscopyas described by Caplan et al (J Am Coll Cardiol. 2006 Apr. 18; 47(8Suppl):C92-6) and fluorescence imaging, such as tagged fluorescentimaging of proteolytic enzymes in tumors (Radiology. 2004 June;231(3):659-66).

Recently, probe designs have emerged that combine multiple imagingmodalities in a single device. Maschke (United States Patent PublicationNo. 2006/0116571 corresponding to U.S. patent application Ser. No.11/291,593) describes an embodiment of a guidewire with both OCT andIVUS imaging transducers mounted upon it. The described invention hasseveral shortcomings. Guidewires are typically 0.014″ to 0.035″ indiameter (approximately 350 microns to 875 microns), yet ultrasoundtransducers typically are at least 400 microns×400 microns and generallyare larger in size for the frequencies in the 20 to 100 MHz range. Ifthe transducer is too small, the beam is poorly focused and has poorsignal properties. In Maschke, the IVUS and OCT imaging mechanisms arelocated at different positions along the length of the guidewire, and asubstantial drawback associated with this type of configuration (havingthe IVUS and OCT imaging means located at different positions along thelength of an imaging shaft) is that optimal co-registration of images isnot possible.

Similarly, U.S. Pat. No. 7,289,842 issued to Maschke describes animaging system that combines IVUS and OCT on a catheter where the IVUSand OCT imaging elements are longitudinally displaced from each otheralong the length of a catheter that rotates around its longitudinalaxis. Maschke also describes generating images where the center portionof the images are substantially derived from the output of the higherresolution OCT imaging portion of the system while the outer portion ofthe images are substantially derived from the output of the ultrasoundimaging portion of the system, to make use of ultrasound's greater depthof penetration in combination with OCT's higher resolution for tissuesclose to the catheter.

U.S. Pat. No. 6,390,978, issued to Irion, describes the use of highfrequency ultrasound in combination with optical coherence tomographywhere the ultrasound beam and the OCT beam are superimposed on eachother.

In U.S. Patent Application Publication No 2008/0177138, Courtney et al.provide an improved multimodal imaging system incorporating both IVUSand OCT transducers in a compact imaging assembly capable ofside-viewing and/or forward-looking imaging. Such multimodal imagingsystems offer the ability to obtain far greater diagnostic informationthan using a single modality imaging device. Indeed, optical coherencetomography generally has superior resolution to ultrasound and has thepotential to better identify some structures or components in vascularand other tissues than ultrasound. For example, fibrous cap thickness orthe presence of inflammatory or necrotic regions near the surface ofarteries may be better resolved with optical coherence tomography.

Unfortunately, many multimodal imaging devices suffer from problemsrelated to incompatibility of one or more imaging modalities with blood.For example, in the case of a multimodal imaging device combining bothIVUS and OCT, the IVUS transducer is capable of functioning with thepresence of blood in the vessel under investigation, but the OCTmodality requires blood displacement. Such a requirement leads tocomplexity of operation and difficulties in coordinating and referencingthe results from the two imaging modalities.

Another problem with the use of multimodal imaging devices is theinaccuracies in co-registration that might result when one imagingmodality is used, followed by another imaging modality after blooddisplacement. For example, intravascular imaging, such as IVUS and OCT,is often used for clinical trial purposes where an imaging protocol isrequired. Manually using one or more modalities to identify regions thatshould be assessed in greater detail by one or more other modality issubject to a substantial amount of operator variability. Furthermore,clinical studies that depend on the ability to compare the structureand/or composition of vessels between different patients or at differenttime points will be dependent on reproducible methods for assessment.

In U.S. Pat. No. 7,758,499, Adler teaches the use of IR imaging withwavelengths of less than 1000 nm, which is minimally compromised by thepresence of blood, in combination with other imaging modalities, such asimaging with visible light. To achieve multimodal optical imaging, blooddisplacement methods are employed, enabling imaging with IR and/orvisible light.

The use of multiple imaging modalities in a single imaging device wasalso recently described by Muller et al. (US Patent ApplicationPublication No. 2009/0299195). Muller describes methods and systems forcombining intravascular ultrasound, optical coherence tomography, andnear infrared spectroscopy for the detection of multiple, differentabnormalities in the arterial morphology during a single intravascularprocedure.

Unfortunately, the known methods employing manual operations forserially acquiring multimodal images require considerable skill andfurther involve complex image spatial alignment operations. Accordingly,there remains a need for multimodal imaging methods that address theaforementioned problems, enable standardized image data acquisition, andprovide improved performance and clinical utility.

SUMMARY

Embodiments of the present disclosure provide systems and methods forimproving the ability to identify and/or collect data from vessels andother tissues with intraluminal probes capable of collecting data usingtwo or more imaging modalities, where one or more imaging modalities arecapable of collecting data through an intraluminal medium (such asblood) and one or more other modalities function with improvedperformance when the intraluminal medium is at least partially displacedfrom the field of view.

In one aspect, there is provided a method of directing a mediumdisplacement operation for performing a minimally invasive procedurewithin a lumen or cavity, the method comprising the steps of: recordinga first set of images obtained from a first imaging modality when afirst translation operation of a functional component of an imagingprobe is performed; spatially correlating the first set of images withan associated position of the functional component of the imaging probe,wherein the first imaging modality is compatible with a presence of adisplaceable medium; processing the first set of images and identifyinga region of interest; and directing a medium displacement operationwhile a second translation operation of the functional component of theimaging probe is performed over the region of interest; wherein theminimally invasive procedure is performed within the region of interestduring the medium displacement operation.

In another aspect, there is provided a method of directing a mediumdisplacement operation for performing a minimally invasive imagingprocedure within a lumen or cavity, the method comprising the steps of:a) obtaining one or more images from a first imaging modality of animaging probe, wherein the first imaging modality is compatible with apresence of a displaceable medium; b) processing the one or more imagesto identify a region of interest; and c) if a region of interest isidentified, directing a medium displacement operation and performing aminimally invasive procedure while the medium displacement operation isperformed.

In another aspect, there is provided a method of directing a mediumdisplacement operation for performing a minimally invasive procedurewithin a lumen or cavity with a probe, the method comprising the stepsof: obtaining, with an external imaging apparatus, one or more images ofa region within which the minimally invasive procedure is to beperformed; identifying a region of interest within the one or moreimages; translating a functional component of the probe to the region ofinterest while obtaining one or more additional images with the externalimaging apparatus, wherein a position of the functional component isidentifiable in the one or more additional images; and directing amedium displacement operation while performing a translation operationassociated with the functional component of the probe within the regionof interest.

In another aspect, there is provided a method of directing a mediumdisplacement operation for performing a minimally invasive procedurewithin a lumen or cavity, the method comprising the steps of: recordinga set of measurements obtained from a non-imaging modality when a firsttranslation operation of a functional component of a probe is performed;spatially correlating the set of measurements with an associatedposition of the functional component of the probe, wherein thenon-imaging modality is compatible with a presence of a displaceablemedium; processing the set of measurements and identifying a region ofinterest; and directing a medium displacement operation while a secondtranslation operation of the functional component of the probe isperformed over the region of interest; wherein the minimally invasiveprocedure is performed within the region of interest during the mediumdisplacement operation.

In another aspect, there is provided a method of directing a mediumdisplacement operation for performing a minimally invasive imagingprocedure within a lumen or cavity, the method comprising the steps of:a) obtaining one or more measurements from a non-imaging modality of aprobe, wherein the non-imaging modality is compatible with a presence ofa displaceable medium; b) processing the one or more measurements toidentify a region of interest; and c) if a region of interest isidentified, directing a medium displacement operation and performing aminimally invasive procedure while the medium displacement operation isperformed.

A further understanding of the functional and advantageous aspects ofthe disclosure can be realized by reference to the following detaileddescription and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will now be described, by way of example only, withreference to the drawings, in which:

FIG. 1 is a block diagram illustrating a system for performingmultimodal imaging.

FIG. 2 is a block diagram illustrating a second system for performingmultimodal imaging incorporating an integrated medium displacementsystem.

FIG. 3 is a perspective drawing showing an example of a multimodalimaging system incorporating both intravascular ultrasound (IVUS) andoptical coherence tomography (OCT), showing a flexible imaging probewith a connector, conduit and imaging assembly;

FIG. 3(a) is a cross sectional view of the mid-section of the imagingprobe of FIG. 1 taken along the dotted line;

FIG. 3(b) is an expanded perspective drawing of the distal region of theimaging probe of FIG. 1;

FIG. 3(c) shows a schematic of how the rotary and non-rotary componentsof the imaging probe can be coupled with an adapter to the rest of animaging system.

FIG. 3(d) is a perspective drawing of an example of the coupling of therotary and non-rotary components of the probe to an adapter.

FIG. 4(a)-(d) illustrates the distal end of an imaging probe that iscapable of both acoustic and optical imaging where a tiltable deflectingsurface can change the imaging angle as a function of the rotationalvelocity of the imaging assembly.

FIGS. 5(a) and 5(b) illustrate an example of a side-viewing multimodalimaging assembly comprising an ultrasound transducer and an opticalfiber for combined co-planar IVUS and OCT imaging.

FIG. 6 is a flow chart describing a method of performing a minimallyinvasive procedure in which results obtained from a first imagingmodality are employed to direct the acquisition of images using a secondimaging modality that benefits from displacement of an intraluminalmedium.

FIG. 7 is a flow chart describing a method of performing a minimallyinvasive procedure in which results obtained from a first imagingmodality are employed in real time to direct the acquisition of imagesusing a second imaging modality that benefits from displacement of anintraluminal medium.

FIG. 8 is a block diagram illustrating a system for performingmultimodal imaging incorporating an integrated medium displacementsystem and an external imaging apparatus.

DETAILED DESCRIPTION

Various embodiments and aspects of the disclosure will be described withreference to details discussed below. The following description anddrawings are illustrative of the disclosure and are not to be construedas limiting the disclosure. Numerous specific details are described toprovide a thorough understanding of various embodiments of the presentdisclosure. However, in certain instances, well-known or conventionaldetails are not described in order to provide a concise discussion ofembodiments of the present disclosure. It should be understood that theorder of the steps of the methods disclosed herein is immaterial so longas the methods remain operable. Moreover, two or more steps may beconducted simultaneously or in a different order than recited hereinunless otherwise specified.

As used herein, the terms, “comprises” and “comprising” are to beconstrued as being inclusive and open ended, and not exclusive.Specifically, when used in the specification and claims, the terms,“comprises” and “comprising” and variations thereof mean the specifiedfeatures, steps or components are included. These terms are not to beinterpreted to exclude the presence of other features, steps orcomponents.

As used herein, the term “exemplary” means “serving as an example,instance, or illustration,” and should not be construed as preferred oradvantageous over other configurations disclosed herein.

As used herein, the terms “about” and “approximately”, when used inconjunction with ranges of dimensions of particles, compositions ofmixtures or other physical properties or characteristics, are meant tocover slight variations that may exist in the upper and lower limits ofthe ranges of dimensions so as to not exclude embodiments where onaverage most of the dimensions are satisfied but where statisticallydimensions may exist outside this region. It is not the intention toexclude embodiments such as these from the present disclosure.

As used herein, the term “high resolution imaging” refers to highresolution imaging methods including, but not limited to, ultrasound andoptical imaging. “High frequency ultrasound” as used herein refers toultrasound imaging with frequencies of greater than about 3 MHz, andmore typically in the range of 8 to 200 MHz.

As used herein, the term “imaging energy” refers to light or acousticenergy or both. Specifically, “light” and/or “optical” refers toelectromagnetic waves with one or more wavelengths that may residewithin in the ultraviolet, visible, near infra-red and/or infraredspectrum.

As used herein, the term “image analysis”, generally refers to theprocessing of image data to identify regions of interest, where theregions of interest general pertain to one or more images or portionsthereof that may be of relevance.

As used herein, the terms “translation” and “translation operation”,when associated with an intraluminal probe such as an imaging probe,refer to the translation of at least a portion of the probe, such that afunctional portion of the probe is translated relative to a lumen inwhich the probe is located. An example of a functional portion of aprobe is an imaging assembly. A translation operation may involvetranslating a functional portion of a probe relative to another portionof a probe, such as an external sheath.

Embodiments of the present disclosure provide systems and methods forperforming improved imaging during a minimally invasive procedure usinga multimodal imaging catheter-based device for which least one imagingmodality benefits from the displacement of intraluminal fluid duringimaging. Specific embodiments provide standardized and/or automatedsystems and methods for selecting regions within a lumen for asubsequent imaging step involving the displacement of an intraluminalmedium.

In one embodiment, a multimodal imaging system is provided that includesat least one imaging modality compatible with imaging in an intraluminalmedium, and at least one imaging modality for which imaging performanceis improved following the displacement of the intraluminal medium.Referring to FIG. 1, a block diagram is shown illustrating an exampleembodiment of a multimodal imaging system 100. The imaging probe 105,which is contained within a lumen that is deliverable to an anatomicstructure 102 (for example, a lumen or blood vessel), includes animaging assembly 110 near its distal end 115, an optional imagingconduit 120 along a substantial portion of its length, and a connector125 at its proximal end 130.

Imaging assembly 110 generally refers to the component of the imagingprobe 105 from which the multimodal signals (for example, acoustic andoptical) are transmitted and/or collected when imaging a region that isproximate to the imaging assembly 110. Multimodal imaging assembly 110includes components and devices for imaging using two or more imagingmodalities. Imaging assembly 110 may include imaging transducers,detectors, and/or imaging energy coupling devices. Imaging energy forirradiating tissue in the vicinity of the probe according to a givenimaging modality may be produced by one or more transducers housedwithin imaging assembly 110, and/or may be produced external to theimaging probe by one or more external transducers and delivered throughan energy guiding device (such as a fiber optic or optical waveguide)through the imaging conduit 120 to imaging assembly 110. Similarly,incident imaging energy produced or scattered within tissue to be imagedand relating to a given imaging modality may be received by a detectorhoused within imaging assembly 110, or may be received within imagingassembly and coupled to an external detector through an imaging energyguiding device within imaging conduit 120. Imaging couplers and relatedenergy guiding devices may support one or more imaging modalities. Forexample, a fiber optic and lens or mirror assembly may be employed forthe delivery of imaging energy related to both OCT and IR imagingmodalities. Imaging energy associated with two or more imagingmodalities may be produced and/or received by a common energy producingand/or receiving apparatus and mutually multiplexed in frequency orinterleaved in time. Imaging probe 105 may be rotatable or may contain arotating imaging element for achieving a radial field of view within alumen.

In embodiments in which at least one imaging modality is opticalimaging, the imaging assembly 110 typically contains the distal tip of afiber optic, as well as a combination of optional optical componentssuch as a lens (such as a ball lens or gradient refractive index lens,also known as a GRIN lens), which collectively serve the purpose ofacting as an optical receiver, (a collection element for collectingoptical energy from the tissue to be imaged) and may also serve as anoptical emitter (a focusing and/or beam directing element for focusingand/or directing an emitted optical beam into the tissue to be imaged).A mirror and/or a prism are often incorporated as part of an opticalemitter and/or receiver. The imaging assembly 110, connector 125 and/orimaging conduit 120 may be immersed in fluid, such as saline. Formultimodal optical and acoustic imaging, imaging probe 105 may becompartmentalized such that there is at least one gas-filled compartmentor lumen for optical imaging and at least one fluid-filled compartmentor chamber for acoustic imaging.

The imaging conduit 120 typically includes at least one opticalwaveguide or at least one conductive wire (optionally two or more) thatconnects an emitter and/or receiver via connector 125 to adapter unit140. Imaging conduit 120 may also act as a mechanical force transmissionmechanism for rotating or translating the imaging assembly. For example,imaging conduit 120 may include a fiber optic, wrapped by two layers ofelectrical wire that are insulated from each other. Imaging conduit 120may be further reinforced by other structural features, such ashelically wrapped wires or other designs used to construct imagingtorque cables for rotating scan mechanisms, as described known to thoseskilled in the art. Imaging conduit may also supply power to amicro-motor located in the distal end of imaging probe 105 for locallyrotating one or more components of imaging assembly 110.

FIG. 3 provides a perspective drawing of an example embodiment of amultimodal imaging probe that may be employed as a component of amultimodal imaging system according to embodiments of the disclosure.The probe shown in FIG. 3 was disclosed in U.S. patent application Ser.No. 10/010,206, titled “Scanning Mechanisms for Imaging Probe” filed onJan. 22, 2008, and U.S. patent application Ser. No. 12/385,014, titled“Scanning Mechanisms for Imaging Probe” and filed on Mar. 27, 2009, thecontents of which are incorporated herein by reference in theirentirety. Briefly, the imaging probe may include an imaging assembly,where the imaging assembly includes a movable member that is capable ofdirecting in imaging energy beam at one or more angles in aforward-looking direction. In two non-limiting example implementations,the orientation of the movable member may be varied by changing therotational velocity of the imaging assembly upon which the movablemember is pivotable, or using a magnetic force or actuation means.

The example imaging probe incorporates both ultrasound (e.g. IVUS) andoptical (e.g. OCT) modalities into a single catheter assembly formultimodal imaging. The system includes a flexible catheter containing afiber optic 40 and a co-axial electrical wire 50. The proximal connectorcontains fiber optic 40 that can be received by the adapter to opticallycouple the imaging fiber optic 40 to the optical imaging system“back-end”. There are also electrical connectors 56 that allow the oneor more electrical conduits to be connected to the electronic or powercircuitry and/or controller and processing units, such as those for anultrasound processing system.

The imaging conduit of the present example rotates around itslongitudinal axis, and the coupling of a rotating fiber optic probe canbe accomplished using a fiber optic rotary joint incorporated either aspart of the proximal connector of the imaging probe 10 or as part of theadapter 14. Similarly, conductive wires that rotate with the imagingconduit are coupled with relatively stationary conductors of theultrasound circuitry and/or controller and processing units, forexample, by means of slip rings or rotary transformers. These slip ringscan be incorporated as part of the proximal connector of the imagingprobe 10 or as part of the adapter 14.

FIG. 3(a) shows a cross sectional view of the midsection of the imagingprobe of FIG. 3 taken along the dotted line which shows a fiber optic40, guide wire port 44 and guide wire 42, imaging conduit 34, imagingconduit lumen 46, external sheath 48 which is a hollow, flexibleelongate shaft made of a physiologically compatible material and havinga diameter suitable to permit insertion of the hollow elongate shaftinto bodily lumens and cavities, and coaxial electrical wiring 50.

The imaging probe may contain ports at one or more points along itslength to facilitate flushing. The expanded detailed view of the end ofthe imaging probe 10 shown in FIG. 3(b) shows the distal end of theguidewire 42 extended beyond the end of the outer sheath 48 and a flushport 54 at the end of the sheath 48.

As shown in FIG. 3, the proximal end of the imaging probe 10 includes aguide wire port 55 into which guide wire 42 is inserted and theconnector assembly 36 which includes a flush port 58 and electricalcontacts 56 along the connector body.

FIG. 3(c) shows a schematic of how the rotary and non-rotary componentsof the imaging probe can be coupled with an adapter to the rest of animaging system. FIG. 3(d) schematically shows how the rotatingcomponents of the imaging probe can be coupled to the rotatingcomponents of an adapter. The rotating components of each can beelectrically, optically and/or mechanically coupled using connectors andother configurations known in the art. Similarly, the non-rotatingcomponents of the imaging probe can be coupled to the non-rotatingcomponents of the adapter 14. The adapter 14 can include slip rings,rotary transformers, optical rotary joints and other such implements forelectrically or optically coupling a rotary component to a non-rotarycomponent and enable communication of necessary electrical and opticalsignals with the rest of the system.

Dual-fiber optical rotary joints are also available but considerablymore complex. Electrical coupling between any conductor mounted onto arotating component in the imaging probe 12 can be coupled tonon-rotating conducting elements via metallic slip rings and springs,metallic slip rings and brushes or other commonly known methods offorming conductive contact between a stationary conductor and a rotaryconductor.

While the electrical, optical and mechanical connections are shownseparately in FIG. 3(d), it is possible to reduce the several connectorsthat must each be separately connected between the probe and adapterwith fewer connectors by combining several connectors into combinedconnectors, as needed for a specific embodiment.

FIG. 4 provides an example of the internal structure of the distal endof the imaging probe that incorporates a multimodal imaging assembly.The assembly includes a tiltable component 70 for deflecting imagingenergy that is emitted and/or received by one or more components thatare not attached directly to the tiltable component 70. An ultrasoundtransducer 88 and optical emitter 92 are provided for directing imagingenergy towards the tiltable component 70. The imaging energy is thendeflected by an energy deflecting component mounted on the tiltablecomponent 70. For ultrasound imaging, the energy deflecting component(the tiltable component 70) may include an acoustically reflectivesurface, such as a solid metal surface (e.g. stainless steel) orcrystalline surface, such as quartz crystal or glass or a hard polymer.

For optical imaging, the energy deflecting component (tiltable component70) may include an optically reflective surface such as a mirror surfacemade from polished metal, metallized polymer such as metallizedbiaxially oriented polyethlylene terephthalate (Mylar), sputtered orelectrochemically deposited metal, metal foil or other reflectivecomponents such as thin film reflectors. Metals commonly used to makemirrors include aluminum, silver, steel, gold or chrome.

An example embodiment of a distal end 29 of an imaging probe 31 is shownin FIG. 4(a), in which the distal end contains an imaging assembly 30that includes a tiltable component 70 where the tiltable component is adisc mounted on pins 72 that enable the disc 70 to pivot about a pin.

The pins 72 define the tilting axis of the tiltable disc 70. When theimaging assembly 30 is at rest, the disc 70 will remain in an arbitrarystarting position. In the example shown, this starting position isdefined by a stop 80 that corresponds to a maximal imaging angle, wherea restoring force providing by a torsion spring 76 is pushing the disc70 towards the aforementioned stop 80. FIG. 4(b) shows a cross sectionalong hashed vertical line 2(c)-2(c) of FIG. 4(a).

If the tiltable component 70 is tilted away from its preferredorientation by an external force, such as gravity, magnetic forces,electrostatic forces, friction with another moving part or fluid,compressive forces, cantilever forces, normal forces or any other sourceof incompletely opposed torque on the tiltable component 70 around thetilt axis, the tilt angle will increase.

One or more stops 80 and 82 may limit the range of the tilt angle of thetiltable component 70. For example, stop 80 may be a post or lipextending from the shell 84 of the imaging assembly 30 as a stop toprevent the tilting component 70 from further changing its tilt anglewhile it makes contact with the stop 80. Therefore, the stop can be usedto limit the tilt angle from exceeding a maximum value determined by theposition of the stop. Once the tilt angle hits this maximum, the normalforce exerted by the stop 80 on the tiltable component 70 opposes therestoring mechanism. In many embodiments, this maximum tilt angle is thetilt angle that is achieved when the imaging assembly 30 is at rest andat low rotational speeds.

An additional or alternative stop 82 can be included to create a minimumtilt angle that the tiltable component 70 will achieve at rotationalspeeds in the upper end of the operating range. Indeed, there are manysituations in which there is no significant benefit in allowing the tiltangle to reach zero, as will become apparent in the followingdescriptions of specific embodiments.

Imaging assembly 30 may include one or more mechanisms that tend tocause the tiltable component 70 to have its tilting angle increase. Forthe purposes of this disclosure, such a mechanism is referred to as arestoring mechanism. The torsion spring 76 (as shown in FIGS. 4(a) and4(c)) or a compression spring can be used as a restoring mechanism,where one end of the spring 76 is mechanically in contact with orcoupled to the tiltable component 70. The other end is mechanicallycoupled to another part of the imaging probe 31, such as the body of theimaging assembly.

As the imaging assembly 30 rotates, the disc 70 will want to alignitself such that the normal of the planes defined by the faces of thedisc 70 are substantially parallel with the longitudinal axis. As seenin FIG. 4(c), the other stop 82 shown (which corresponds to a minimumimaging angle) will prevent the disc 70 from reaching its preferredorientation at high rotational speeds of the imaging assembly. With asuitably configured imaging assembly, the stop 82 that corresponds to aminimum imaging angle can correspond to an angle of zero, providingimaging in a direction parallel to the longitudinal axis of the imagingprobe.

Another example of a multimodal imaging assembly for use in a multimodalimaging system is provided in FIGS. 5(a) and 5(b), as taught in U.S.patent application Ser. No. 12/010,208, titled “Imaging Probe withCombined Ultrasound and Optical Means of Imaging”, filed on Jan. 22,2008 by Courtney et al., which is incorporated herein by reference inits entirety. Referring to FIG. 5(a), an imaging assembly 550 isprovided which is configured to allow imaging by acoustic and opticalmeans in the same direction, so that an acoustic transducer that allowslight energy to travel through a channel in the transducer is utilized.Essentially, assembly 550 uses an acoustic transducer 502 that isaltered to have an optically transmissive channel made through itssubstrate. The acoustic transducer 502 can be any kind of ultrasoundtransducer known in the art, such as piezoelectric composition (e.g. PZTor PVDF, single crystal piezoelectric), a composite transducer or acapacitive micromachined ultrasonic transducer (cMUT).

Electrical conductors 500 are directed to the conducting layers 501 oneither side of the transducer's acoustic substrate 502. A fiber optic503 provides an optical conduit for enabling optical imaging. One ormore matching layers can be added to the emission surfaces of thetransducer, such as an epoxy layer (such as a silver or copperconductive epoxy layer which may functionally also serve as one or bothof the electrodes that drives the transducer), or a polymer (such asparylene or PVDF).

Conductive layers 501 on either side of the piezoelectric material 502are incorporated as required for applying a voltage to thepiezoelectric. The opening 507 is coupled to an optical waveguide 503,either directly, or by means of one or more mirrors or prisms and one ormore lenses (not shown). If any optical components are included withinthe opening, a dampening, insulating layer of a compliant material 506,such as silicon or polymer may separate the optical components from theacoustic substrate 502 to act as either an electrical insulator or tominimize the transmission of stresses that are generated by the acousticsubstrate 502 to the optical components.

As shown in FIG. 5(b), the light from the fiber can be directed towardsa mirror 404 (or prism) that causes the light from the fiber to bedeflected through the optically transmissive channel 507.

Yet another non-limiting example of a multimodal imaging system isprovided in FIG. 1 of US Patent Publication No. 2009/0299195, titled“Multimodal Catheter System and Method for Intravascular Analysis”, andfiled by Muller et al., of which only FIG. 1 is incorporated herein byreference. The system combines intravascular ultrasound, opticalcoherence tomography, and near infrared spectroscopy for the detectionof multiple, different abnormalities in the arterial morphology during asingle intravascular procedure.

The above examples illustrate multimodal imaging systems, which may beadapted according to embodiments of the present disclosure as describedbelow. It is to be understood that the preceding examples were merelyprovided as a non-limiting examples, and that other multimodal imagingprobes may also be used with embodiments of the present disclosure.

Referring again to FIG. 1, multimodal imaging system 100 is configuredfor the displacement of an intraluminal medium during a non-invasiveprocedure to support an imaging modality that benefits from thedisplacement of intraluminal medium during imaging. Such displacementmay be provided and controlled by one of many devices and subsystems,including, but not limited to, subsystems for displacement ofintraluminal medium through intraluminal flushing, and subsystems fordisplacement of intraluminal medium through controlled occlusion of thelumen, as taught in US Patent Publication No. 2009/0299195 and U.S. Pat.No. 7,758,499, titled “Method and Apparatus for Viewing Through Blood”,which is incorporated herein by reference in its entirety.

In one embodiment, intraluminal flushing may be achieved by providingflushing liquid to the imaging probe 105 through an input port, wherebythe flush liquid is dispensed into the lumen via output ports providedat one or more points along the length of imaging probe. Alternatively,flushing liquid may be provided via a conventional guide catheter thatis able to introduce fluid into the lumen to be imaging. Alternatively,flushing liquid may be provided via a specialized flush catheter, forexample, as disclosed in U.S. Pat. No. 7,625,366, titled “Flush Catheterwith Flow Directing Sheath”, which is incorporated herein by referencein its entirety. Flushing liquid, such as a saline solution, Ringer'slactate solution or contrast agent, may be provided manually, forexample, using an external syringe. In some example embodiments,flushing may be performed via an auto-injector, pressure infuser bag, aperistaltic pump, a syringe or piston pump; a valved system, a gravitypressurized system, and the external application of pressure to mediumusing automated or manual application of pressure.

In one embodiment, medium displacement apparatus, shown generally at135, provides and/or regulates or controls one or more mediumdisplacement operations. As noted above, medium displacement apparatus135 may be interfaced with imaging probe 105, or may be provided as aseparate apparatus (such as a guide catheter or specialized flushcatheter) for achieving medium displacement. In a non-limiting example,medium displacement apparatus 135 may include an external pump (notshown) that provides controlled volumes of flush solution (from areservoir) to a region of interest. In another example, mediumdisplacement apparatus 135 may include an inflatable balloon housed onor within imaging probe 110 for achieving medium displacement bycontrolled inflation that results in full or partial occlusion of thelumen.

In another embodiment, medium displacement apparatus 135 may furtherinclude an external manual switch that only enables or authorizesautomated displacement operations when the switch is activated by a useror physician. Such a switch enables a supervisory mode of semi-automatedmedium displacement, requiring that a human operator is activelyinvolved in monitoring any automated displacement operations.Non-limiting examples of suitable switches include a button or a footpedal that must be continuously depressed for automated displacement(e.g. injection or inflation) to take place.

Referring again to FIG. 1, driver and adapter unit 140 includesinterfaces for facilitating transmission of power and/or signals withinany fibers and/or wires between imaging probe 105 and the appropriatecontrol and/or processing subsystems. It may include a motor driversubsystem 145 for imparting rotation motion to rotary components of theimaging probe. Motor drivers may also power a pullback mechanism,push-forward mechanism or a reciprocating push-pull mechanism tofacilitate longitudinal translation of imaging assembly 110. Suchlongitudinal translation of imaging assembly 110 may occur inconjunction with the longitudinal translation of an external shaft (notshown) that surrounds the image assembly 110 and imaging conduit 120, ormay occur within a relatively stationary external shaft.

Additional sensor subsystems may be incorporated as components of thedriver and adapter unit 140, such as a position sensing subsystem 150,for example to sense the angle of rotation of a rotary component withinimaging probe 110 and/or the longitudinal position of imaging assembly110. Imaging probe 110 may also include a memory component such as anEEPROM or other programmable memory device that includes informationrelating to imaging probe 110 such as, for example, identifyingspecifications of imaging probe 110 and/or calibration information.Additionally, driver and adapter unit 140 may further include amplifiers160 to improve the transmission of electrical signals or power betweenimaging probe 110 and the rest of the system.

Driver and adapter unit 140 is interfaced with control unit 165. Controlunit 165 includes first 170 and second 175 imaging modality controllersubsystems to support the multimodal imaging devices (the system mayfurther include additional imaging modalities and controllers inaddition to the two shown), which may include, but are not limited to,any of the following imaging modalities: 1) ultrasound, 2) opticalcoherence tomography, 3) angioscopy, 4) infrared imaging, 5) nearinfrared imaging, 6) Raman spectroscopy-based imaging and 7)fluorescence imaging.

While the first and second imaging modality controllers are shown asseparate subsystems, it is to be understood that they may be one and thesame. For example, OCT and near infra-red (NIR) spectroscopy data canconceivably be acquired via a common light source and signal acquisitionsystem. Similarly, when the first and second modalities are both IVUS,with one modality being a lower frequency IVUS than the other, thehardware required to generate and acquire the two sets of IVUS data maybe the same, with different operating parameters.

An optical modality controller may include any or all of the followingcomponents: interferometer components, one or more optical referencearms, optical multiplexors, optical demultiplexers, light sources,photodetectors, spectrometers, polarization filters, polarizationcontrollers, timing circuitry, analog to digital converters and othercomponents known to facilitate any of the optical imaging techniquesdescribed herein or incorporated herein by reference.

An ultrasound modality controller may include any or all of thefollowing components: pulse generators, electronic filters, analog todigital converters, parallel processing arrays, envelope detection,amplifiers including time gain compensation amplifiers and othercomponents known to facilitate any of the acoustic imaging techniquesdescribed herein or incorporated herein by reference. Control unit 165may include one or more of the following non-limiting list ofsubsystems: a motor drive controller 180, position sensing controlcircuitry 190, timing circuitry, volumetric imaging processors, scanconverters and others.

As shown in FIG. 1, medium displacement apparatus 135 may be operatedand/or controlled independent of control unit 165. For example, mediumdisplacement apparatus 135 may include a syringe or a manual pump. Inanother embodiment, shown in FIG. 2, control unit 165 may furtherincludes medium displacement controller 185, which monitors mediumdisplacement operations and may also automate or semi-automate mediumdisplacement operations. In an alternate embodiment, medium displacementcontroller 185 may be directly interfaced with medium displacementapparatus 135. Medium displacement controller 185 may monitorinformation including, but not limited to, a volume of flush solutionprovided for a given medium displacement operation, a total of flushsolution provided for multiple medium displacement operations for agiven patient and/or minimally invasive procedure, a time durationduring which a given medium displacement operation is carried out, atotal time duration over which multiple medium displacement operationsare carried out for a given patient and/or minimally invasive procedure,and control signals and/or commands communicated to a device orsubsystem for achieving medium displacement.

Medium displacement controller 185 may provide input to a feedback loopemployed during control of a sequence of imaging and displacementoperations coordinated by processing unit 205, as further describedbelow.

Control unit 165 may further include an optional cardiac sensorcontroller 195 for controlling optional cardiac sensors 200, such aselectrode sensors to acquire electrocardiogram signals from the body ofthe patient being imaged. The electrocardiogram signals may be used totime the acquisition of imaging data in situations where cardiac motionmay have an impact on image quality. The electrocardiogram may alsoserve as a trigger for when to begin an acquisition sequence, such aswhen to begin changing the speed of rotation of a motor in order tocause a desired scan pattern to take effect. For example, ECG-triggeredinitiation of an imaging sequence may enable images to be acquiredduring a particular phase of the cardiac cycle, such as systole ordiastole. The electrocardiogram signals optionally serves as a triggerfor varying the rate of injection or inflation of the mediumdisplacement system to allow the system to account for the pulsatilenature or blood flow under observed physiological conditions.

Control unit 165 is interfaced with processing unit 205, which includesa processor 210 and memory and/or storage subsystem 215 connected by abus, and performs multiple processing functions for coordinating variousaspects of system operation. It is to be understood that althoughcontrol unit 165 and processing unit 205 are shown as distinctsubsystems, they may be provided in a composite computing system 220.Furthermore, some or all of the elements of control unit 165 may beperformed by processing unit 205. Furthermore, processor 210 may includeseveral processing elements, such as one or more CPUs, fieldprogrammable gate arrays, GPUs, ASICs, DSP chips and other processingelements known in the art. Processing unit 205 may also be interfacedwith display and user interface 225 for either real time display ordisplay of data at a time later than the time at which imaging data isacquired.

Imaging system 100 may further include data storage components (such asmemory, hard drives, removable storage devices, readers and recordersfor portable storage media such as CDs and DVDs), which may beinterfaced with components of the processing unit and/or control unit.

In one embodiment, processing unit 205 is programmed to analyze imagesobtained using a first imaging modality, and to utilize the imagingresults to automate the recording of images based on a second imagingmodality that requires or benefits from an intraluminal mediumdisplacement operation during image acquisition. The first imagingmodality may be compatible with intraluminal medium, such that it doesnot require an intraluminal displacement operation to images withsufficient diagnostic sensitivity or clinical utility.

In an embodiment in which the intraluminal liquid is blood, the firstimaging/detection modality may be selected from the non-limiting listincluding grayscale IVUS, radio-frequency IVUS (e.g. Virtual Histology™,integrated backscatter or iMap™), elastography, NIR spectroscopy,sono-luminescent imaging, microbubble enhanced IVUS, targetedmicrobubble enhanced IVUS, photo-acoustic imaging, fluorescencespectroscopy, biosensors such as ion-selective field effect transistors,and the second imaging modality may be selected from the non-limitinglist including OCT, angioscopy, NIR spectroscopy, Raman spectroscopy,IVUS, radio-frequency IVUS, elastography, sono-luminescent imaging,microbubble enhanced IVUS, targeted microbubble enhanced IVUS,fluorescence spectroscopy, and photo-acoustic imaging. A second imagingmodality that is optical in nature may utilize wavelengths from theultraviolet, visible, NIR, and/or infrared portions of theelectromagnetic spectrum.

In another embodiment, the first and second imaging modalities may be asingle imaging modality, for which images may be initially obtained inthe presence of an intraluminal medium, and where improved images may besubsequently obtained via a displacement operation.

Even though ultrasound has reasonable penetration through blood, thedisplacement of blood from the field of view of an ultrasound imagingprobe can still improve the ability to identify the wall of a vessel orprovide improved image contrast. Meanwhile, ultrasound has the abilityto better penetrate through biological media such as blood and softtissues and has a depth of penetration that typically extends severalmillimeters or centimeters beyond that of optical coherence tomography.

In one example embodiment, the first and second imaging modalities areboth IVUS, but the first modality is IVUS having a lower frequency rangethan the second IVUS modality. Generally speaking, higher frequencies ofultrasound provide higher resolution than lower frequencies, but higherfrequencies do not penetrate through blood as well. Therefore, it may bedesirable to displace blood when imaging with higher frequencies ofIVUS. There may be separate ultrasound transducers for the two IVUSimaging frequencies, or the ultrasound transducers may have a wideenough bandwidth to be able to support two or more imaging frequencies,where the imaging frequencies are dictated in part by the frequency ofthe pulses used by a pulser to excite the ultrasound transducer.

The ability to combine ultrasound with optical imaging methods, such asOCT or near infrared spectroscopy using a single imaging probe, providesadvantages with respect to selecting the required resolution and depthof penetration. Furthermore, much of the information acquired by opticalcoherence tomography is complementary to that acquired by ultrasound andanalysis or display of information acquired by both imaging methodswould improve the ability to better understand the interrogated tissue,such as with respect to its composition.

It should be noted that while intravascular OCT is significantly impededby the presence of blood, NIR spectroscopy is less affected and is ableto assess plaque composition up to a distance of a few millimetersthrough blood. However, it will be less effective in larger vessels andaneurysmal segments of otherwise normal-calibre vessels.

Referring to FIG. 6, a flow chart is provided that illustrates anembodiment in which images recorded using a first imaging modality areemployed to direct a displacement operation when subsequently obtainingimages from a second imaging modality, where the second imaging modalityis impeded by the presence of a displaceable intraluminal medium.

In step 300, a multimodal imaging probe, such as imaging probe 105 inFIG. 1, is inserted into a lumen for obtaining images with a firstimaging modality that is compatible with the presence of a displaceableintraluminal medium. A first imaging operation, which may be atranslation operation such as a pullback, is performed while recordingimaging data using the first imaging modality. The translation operationmay be automated and performed at a constant translation rate that isselected and/or optimized for the first imaging modality. Signalsobtained from the first imaging modality device (located in imagingassembly 110 of imaging probe 105) during the first translationoperation are provided to first imaging modality controller 170.

According to the present embodiment, position sensing is employed duringthe translation operation to identify the location of the recordedimages relative to a reference position and optionally a referenceorientation. The recorded images are therefore correlated with theposition, and optionally the orientation, of the imaging probe. Positionsensing may be achieved using one of many known methods, and isgenerally represented in FIG. 1 by position sensor 150 and positionsensing controller 190 (which may together form a composite subsystem).

In one embodiment, position sensing is obtained by intraluminallongitudinal position sensing, for example, using encoders or otherposition sensors connected to the imaging probe, pullback motor or driveelement. Position sensing may be obtained via spatial domainmeasurements, or inferred based on time-domain measurements in whichtranslational or rotatory motion is performed at known rates. Forexample, position information relating to the longitudinal position ofan imaging probe may be inferred based on a time interval over whichtranslation occurs, provided that the rate of change of the position ofthe image probe is known during the time interval. The rate of change ofposition may be constant during probe translation. Angular orientationsensing may be obtained using rotary encoders or other position sensorsconnected to the imaging probe, as taught in co-pending U.S. patentapplication Ser. No. 12/010,207, titled “Medical Imaging Probe withRotary Encoder” and filed on Jan. 22, 2008, which is incorporated hereinby reference in its entirety.

In another embodiment, position sensing may be achieved using a sensingelement located in the imaging probe that determines the location of theimaging probe in an externally created field, such as a magnetic field,which may be performed in combination with orientation sensing. Asuitable sensor is provided by Mediguide Ltd., and may be employed astaught by Muller et al. in US Patent Application Publication No.2009/0299195.

After having performed a first translation operation, image data fromfirst imaging modality controller 170 is provided to processor 210 forimage analysis in step 305. Processor 210 analyzes the image dataaccording to an image processing algorithm to, identify regions ofinterest, such as regions of diagnostic, research, and/or clinicalinterest. Regions identified may represent a wide range of anatomicalstructures and/or features, including, but not limited to, a desiredtissue type for subsequent analysis, specific anatomical features, knownor suspected pathological structures or features, and medical implantsor other artificial structures. Suitable regions of interest include thefollowing non-limiting list: plaque, possible thrombus, branch points,lesions, calcifications, implants such as stents or brachytherapyimplants, stenoses, areas of vessel wall thickening, lipid cores,necrotic regions, fibrous caps, dissections, masses and the like.Regions of interest may further include regions with microbubblesdetected, such as targeted microbubbles. They may also include regionsof indeterminate or uncertain structure or composition, where anautomated or semi-automated processing algorithm cannot confidentlyassess the region of interest without further imaging data.

Regions of interest may further include vascular lesions that have notled to clinical symptoms, but are at increased risk of rupturing oreroding and causing an acute myocardial infarction. These so-called“vulnerable plaques” are an area of interest as the prospect of treatingsuch plaques to pre-empt adverse clinical events is conceptuallyappealing.

In another embodiment, a region of interest may be identified as anyregion where indeterminate results are suspected from any imagesobtained based on the first imaging modality. For example, when NIRspectroscopy is used as the first imaging modality, a region of interestmay be defined for a region where the vessel wall is further from theimaging assembly with the imaging probe than allowed by the range of anNIR spectroscopy probe in the presence of blood. Alternatively, such aregion may be defined for the case of IVUS imaging when the vessel wallis in contact with the imaging probe. IVUS can be subject to severalartifacts in portions of the field of view closest to the catheter.These include a phenomenon known as transducer ring-down, as well asartifacts that arise from ultrasound reflections from the cathetersheath. OCT is substantially less affected by such artifacts and iscapable of providing excellent images of portions of the field of viewthat are closest to the catheter.

In one embodiment, a region of interest may include a stent having aknown geometrical shape, structural form and/or imaging signalcharacteristics. This could include metallic stents, polymeric stents,biodegradable stents, pacemaker wires, guidewires and the like.

Regions of interest may be identified using one of many known imageanalysis methods. Regions of interest may be identified by processingimages to obtain metrics that can be compared with expected values orranges. In another example implementation, image analysis is performedin combination with a pattern recognition method for identifying theregions of interest. In one example, the imaging analysis methodincludes border detection. For example, border detection may be employedfor the detection of regions with plaque thickening that are suitablefor subsequent imaging by the secondary imaging modality. Borderdetection may be achieved by a number of different methods. In onenon-limiting example, border detection is described by Papadogiorgaki etal. using the contour optimization technique (Ultrasound in Medicine andBiology 2008, September 34(9) 1482-98). For example, methods of borderdetection are taught in U.S. Pat. No. 7,359,554, titled “System andMethod for Identifying a Vascular Border” and US Patent Publication No.2005/0249391, titled “Method for Segmentation of IVUS Image Sequences”,both of which are incorporated herein by reference in their entirety.

In one embodiment, regions of interest are identified by imageprocessing methods that involve tissue characterization techniques. Forexample, in applications in which the first imaging modality is IVUS ora variant thereof, regions of interest may be determined by theradio-frequency properties of the backscattered ultrasound signalcombined with a pattern recognition algorithm, as taught by Nair in U.S.Pat. No. 6,200,268, which is incorporated herein by reference in itsentirety. Tissue characterization techniques may alternatively employanalysis of the intensity of grayscale pixels. For example, certainintensity ranges of pixels in the generated images are more likely torepresent soft plaque that may further include lipid-rich regions.Alternatively, texture analysis algorithms, such as waveletdecomposition algorithms or algorithms that assess statisticalproperties the imaging data may be used. Alternatively, heuristicalgorithms that detect known properties of certain tissue components maybe utilized. For example, an algorithm may detect acoustic shadowing,which is known to correlate well with the presence of calcifications inIVUS imaging.

It may be desirable to input several imaging data parameters into apattern recognition algorithm that is able to identify the most likelytissue composition for a particular region. Such a pattern recognitionalgorithm could be a neural network, fuzzy logic algorithms, a dataclassification tree, nearest neighbor techniques, and several otherpattern recognition techniques. Such a pattern recognition algorithm maybe trained using imaging data for which the true underlying compositionof the tissue is known, such as by any combination of histology,radiography, spectroscopy, ultrasound, optical imaging and others. Sucha pattern recognition algorithm may identify not only the most likelyunderlying tissue composition for a given region of interest, but alsoprovides an estimate of its likelihood of being correct. Alternatively,the pattern recognition algorithm can simply identify regions for whichthe underlying composition with the first imaging modality is uncertain,prompting the need for additional analysis with a second imagingmodality.

Regions of interest may additionally or alternatively be determinedbased a non-imaging modality, such as based on temperatureheterogeneity. An example method of detecting thermal heterogeneity isprovided in Stefanidis C, et al., “Thermal heterogeneity within humanatherosclerotic coronary arteries detected in vivo: a new method ofdetection by application of a special thermography catheter”,Circulation 1999; 99; 1965-71. A temperature sensor may be incorporatedinto the distal region of probe 115 to detect a change in thetemperature of the wall of the artery, where higher temperatures arethought to more likely correspond to inflammatory regions. In yetanother embodiment, regions of interest may be defied based on regionshaving a minimum concentration of a locally detected biological analyte,such as markers of inflammation, for example detecting C-reactiveprotein (CRP) by a local biosensor such as an ion-selective field effecttransistor (ISFET) having bound thereon a selective detection speciessuch as an antibody or aptamer.

The aforementioned automated systems and methods for identifying regionsof interest for further analysis by the second imaging modality mayinclude settings that enable a user to adjust or vary the parametersthat influence the identification of regions of interest. For example,such settings may enable the user to select specific pathologicalfeatures or structures, such as the identification of regions having atleast a selected amount of plaque, or a selected minimum vessel wallthickness, or a selected degree of eccentricity in the wall thickness.It is known that plaques are unlikely to reside in regions where thereis minimal thickening of the vessel wall and that plaques tend to residein regions where there is eccentric thickening of the vessel wall.

In another embodiment, the one or more threshold parameters that triggerthe identification of a region of interest may be configurable. Such anembodiment is particularly important for applications in which contrastagent, saline solution, or another flush solution is dispensed during amedium displacement operation. By controlling the one or more thresholdparameters for which a region of interest is identified, a clinician oroperator may be able to control or limit the volume of flush solutiondelivered during a minimally invasive procedure to ensure that thevolume of flush solution employed has a controlled or minimal impact onthe patient.

Although the aforementioned embodiments involve automated methods ofidentifying a region of interest, it is further contemplated thatregions of interest may be manually defined by a user or operator byreviewing the results of images obtained via the first translation (e.g.pullback) operation, and selecting regions of interest for a secondautomated or semi-automated secondary translation operation in which theregions of interest are imaged via the secondary imaging modality whileperforming medium displacement operations, as further described below.

A region of interest may also be defined or identified according to morethan a single imaging modality. For example, the imaging probe mayinclude multiple imaging modalities that are compatible with thepresence of an intraluminal medium, and the region of interest may beidentified by processing the multiple imaging modalities according tothe methods described above.

Referring again to FIG. 6, after having obtained one or more regions ofinterest in step 305, regions of interest to be imaged during a secondpullback operation with the second imaging modality are selected in step310. This step may include automatically selecting all regions ofinterest identified in step 305, or alternatively, this step may includeselecting a subset of the regions of interest identified in step 310. Inthe latter case, the selection of the subset of regions of interest maybe performed by a user operating the system via user interface 225, ormay be achieved by pre-selecting types of identified regions that aredesired for subsequent analysis.

For example, although regions of interest may be identified in step 305that relate to a wide range of normal anatomical structures, implants,tissue types, and pathological structures or signatures, the system maybe configured to only image a detected implant using the second imagingmodality. Alternatively, the system may rank the regions of interestidentified in step 305 according to any of several criteria, such as,but not limited to, plaque size, predicted likelihood of being athin-capped fibroatheroma, location in the vasculature and others. Oncethe regions of interest are ranked, a subset may be selected, such as agroup of the regions of interest that ranked highest according to thecriteria used.

Having selected the regions of interest for imaging via the secondimaging modality (either automatically or via user intervention), asecond pullback operation is then performed to image the selectedregions of interest. This operation may be performed according to anumber of embodiments, as further disclosed below.

Initially, the imaging probe (and/or a functional component thereof) istranslated to a region of interest selected in step 315. The translationmay be performed manually, with feedback from the position sensingsystem to determine when the probe has been moved to the appropriatelocation, and may additionally or alternatively involve the automatedtranslation of the imaging probe to position the imaging assembly in therequired location.

Image comparison techniques may assist or guide the automatedtranslation of the imaging probe to the desired position.Cross-correlation techniques can be used to identify images or regionswithin an imaging dataset that are similar to each other. In itssimplest form for a 2D image, this involves multiplying the intensity ofeach pixel in one image with the intensity of the corresponding pixel inanother image, and calculating the sum of these products. A highlysimilar image will have a high sum of products. By repeatedly shifting,rotating and/or morphing one of the images with respect to the other andrepeating the cross-correlation calculation, an assessment for thesimilarity of the two images can be made that takes into account thesetransformations.

Cross-correlation techniques can be extended to 3D imaging datasets oralternatively be focused on localized regions within 2D imagingdatasets. Cross-correlation techniques can be applied to 2D imagingdatasets that are derived from 3D imaging data. For example, rather thanapplying cross-correlation to cross-sectional images, 2D longitudinalimages generated by extracting data in any plane from a series of 2Dcross-sectional images that are stacked together to form a 3D datasetcan be used. In the present embodiments, cross-correlation of apre-selected image or imaging dataset corresponding to a start or stoppoint identified on a first pullback can be applied to imaging databeing acquired during a second pullback to better identify the start orstop points for media displacements operations.

Prior to obtaining images via the second imaging modality, adisplacement operation is initiated in step 325 for displacing thedisplaceable medium within the lumen, to support imaging via the secondimaging modality. As described above, any suitable displacementoperation may be performed, including, but not limited to, flushing orinflation. The displacement operation may be initiated prior to thecompletion of the translation step 320 such that the system anticipatesthe time at which a selected region of interest will be assessable bythe second imaging modality, and that the displacement operation has hadthe desired effect of adequately displacing the intraluminal media bythe time the translation step 320 results in the imaging probe beingpositioned properly for the second imaging modality to assess theselected region of interest with minimal or no time delay. Whiledisplacing the medium, a pullback operation is performed in step 330 forimaging the region of interest using the second imaging modality.

In one embodiment, when performing step 330, in which a translationoperation is performed to obtain images from the second imagingmodality, additional images may be obtained from the first modality toaccommodate or correct for positional errors or disturbances, such astissue motion and/or errors in position detecting system. If the imagingmodalities are accurately co-registered, acquiring images concurrentlywith the first and second modality will provide images at the samelocation, without introducing errors from tissue motion (i.e. cardiac,respiratory, etc). In one embodiment, the displacement operation,pullback operation, and imaging operations are automated by the imagingsystem to image the selected region of interest. The displacementoperation may be performed continuously during the second pullbackoperation, or may be performed over discrete time or distance intervals.The automated dispensing operation may be activated or enabled by a userduring steps 325 and 330, for example, by continuously activating aswitch such as a button or foot pedal. Such a supervisory mode ofimaging automation assists in ensuring that all medium displacementoperations are performed in the presence of an operator. The operatormay interrupt the process, for example, if it is deemed that a volume offlush solution employed has exceeded a pre-selected amount.

In alternative embodiments, one or more of steps 330 and 335 may bemanually performed. In one embodiment, both steps 330 and 335 aremanually performed, and the positions at which to perform thedisplacement operation and imaging operations are suggested to a userbased on the selected regions identified in step 315. For example, anoperator may translate the imaging probe, and the system (for example,via user interface 225) may indicate to the user positions at whichdisplacement and imaging are to be performed. The user may then manuallyperform a displacement operation using a manually actuated mediumdisplacement apparatus 135 as shown in FIG. 1.

In another embodiment, the operator may manually translate the imagingprobe, and the imaging system may perform automated dispensing andimaging when the imaging probe passes the regions of interest selectedin step 315 (for example, using the integrated medium displacementapparatus 135 in FIG. 2, and related monitor/driver and controllercomponents of the system.

In yet another example implementation, the imaging probe may betranslated in an automated fashion, and the imaging system may indicateto the operator the locations at which a displacement operation isrequired for obtaining images via the second imaging modality. In suchan embodiment, the system may automate the acquisition of images usingthe second imaging modality whenever a displacement operation ismanually performed by the operator.

In one embodiment, the displacement operation is monitored, for example,by medium displacement monitor 155 shown in FIG. 2. As noted above, theparameters monitored may include a volume of flush solution provided fora given medium displacement operation, a total of flush solutionprovided for multiple medium displacement operations for a given patientand/or minimally invasive procedure, a time duration during which agiven medium displacement operation is carried out, a total timeduration over which multiple medium displacement operations are carriedout for a given patient and/or minimally invasive procedure, and controlsignals and/or commands communicated to a device or subsystem forachieving medium displacement.

In one embodiment, a monitored displacement parameter is employed toprovide feedback to the imaging system. The system may be provided withthreshold ranges or maximum values for monitored displacementparameters. Exceeding such threshold values may trigger a visible oraudible alarm. Alternatively, exceeding a threshold may result inautomatic suspension or termination of a given displacement operation(and optionally alerting an operator of the event). Monitoreddisplacement parameters may be stored and made available to an operatoror clinician following a minimally invasive procedure, for example, tobe included in documentation relating to the procedure. Alternatively,monitoring of a displacement operation may be employed to determine atime interval or a distance interval over which to perform steps 325 and330. For example, after translating the imaging probe to a region ofinterest in step 320 and initiating a displacement operation in step325, the imaging probe may be further translated while imaging anddisplacing the intraluminal medium until a monitored displacementthreshold is exceeded.

It may be desirable to utilize feedback from the processed images in theabove embodiments to control and/or optimize the rate of translationand/or rotation of the imaging probe. The pullback or push-forwardspeed, and/or the rotational speed of a torque cable may be controlledby the processing unit 205 and/or the controller unit 165. These speedsmay be modified, determined and/or optimized separately for each imagingmodality. Additionally, the speeds may be modified based on imagesprocessed by processing unit 205. For example, when assessing the imagesobtained by the first imaging modality, if the first imaging modalitydetects a region where the second imaging modality is to be activated,it may be desirable to increase the speed of pullback and/or the speedof rotation of the torque cable while the second imaging modality (forexample, OCT) is being used. Speeding up image acquisition duringoperation of an imaging modality that requires displacement ofintraluminal media may help reduce the duration of displacement or theamount of displacing media, such as contrast, that would need to beintroduced while images are obtained.

In one embodiment, it may be desirable to selectively disable one ormore of the imaging modalities as the speed of rotation or the speed oftranslation are adjusted. For example, a first modality may identify aregion of interest that initiates a media displacement operation,activates a second imaging modality, changes the speed of rotationand/or changes the speed of pullback. If the first modality is renderedless useful by operation at a different speed of rotation and/or speedof pullback, it may be desirable to temporarily disable the firstmodality until a controller determines that the second modality is to bedeactivated.

For example, if IVUS is the first imaging modality, the system mayoperate at a rotational speed in the range of 5 to 100 frames per secondduring IVUS analysis, in which IVUS identifies a region of interest.However, while imaging with a second imaging modality, such as OCT, therotational speed may be increased to greater than 50 frames per secondand the pullback speed may be increased to greater than 2 mm/s. Whilethe limits of rotational speed for useful IVUS image acquisition areimplementation specific and application specific, it is recognized thatit may be reasonable to either disable or discard IVUS images during OCTacquisitions that employ rapid rotational speeds. In such a case, theend of the region of interest can be identified by the second imagingmodality or any of several previously mentioned parameters that do notrely on the first imaging modality to identify the endpoint of a regionof interest, such as time expired, volume of displacement media used orreaching a known position based on position sensor data from thepullback mechanism.

In yet another embodiment, during steps 325 and 330, image processing ofthe images obtained using the second imaging modality may be performedin real-time to assess the quality of the images. For example, imagequality may be assessed by comparing the intensity, signal attenuationor texture of sections of the image, such as sectors, to pre-set desiredranges or thresholds. The images may be analyzed, for example, by theprocessing unit 205, to ensure that the border of the anatomic structureis relatively or sufficiently contiguous (for example, as defined by apre-selected metric), with a well delineated border between the vesselwall and the lumen, as would be expected with adequate flushing.

Alternatively, sections of the image can be analyzed to detect or inferthe presence of an intraluminal medium such as blood. Blood willtypically have a signature or range of appearances for each modality,whether it be based on signal intensity, signal attenuation or, in thecase of NIR imaging, spectral content. The quality of the image can beascertained, at least in part, by ensuring that the signature of bloodis not present in each section of the image from which it is desired tohave blood displaced.

The perceived image quality may then be employed to provide feedback tostep 325 and regulate the medium displacement operation. For example, ifan image is deemed to be characterized by a poor signal-to-noise ratio,the rate of delivery of flush solution, volume of flush solution, timeprofile of amount flushed, or the volume of inflation for a displacementballoon, may be varied.

Alternatively, data from a non-invasive imaging modality may be used toassess the adequacy of displacement of intraluminal media. For example,an angiogram can be processed in real time or shortly after thedisplacement means is activated and the resulting images can beprocessed to determine if the vessel is fully opacified by contrastmedia. This determination can be done by assessing the change in pixelintensities of the angiogram or by assessing the sharpness of vesselborders in the angiogram.

In one embodiment, the image quality obtained by the second imagingmodality is assessed in real time, and feedback provided to regulate aparameter related to the displacement operation in order to minimizeaspects of the displacement operation. The image quality may be assessedto minimize the time of a displacement operation, the rate of deliveryof a flush solution, and/or the volume of flush solution.

In another embodiment, the second pullback operation in step 330 may beinitiated once the field of view is adequately improved with flushingbased on real time image analysis, after which the imaging probecontinues to translate for the acquisition of images until the end ofthe region of interest. If, in that time period, the field of viewprovides inadequate image quality, the pullback controller may stopand/or step-back, and resume translation once the field of view isadequate based on the assessment of image quality.

After having performed step 330 and obtained images of a given region ofinterest using the second imaging modality, the steps 320 to 330 may berepeated as indicated at 335 to obtain images of additional regions ofinterest selected in step 315. Accordingly, the method may be performedby performing a full pullback operation in step 300 to identify andselect regions of interest, followed by serial pullback and displacementoperations in steps 320 to 330 to acquire images for the selectedregions of interest using, the second imaging modality.

In an alternative embodiment, the initial pullback operation 300 mayperformed as a partial pullback operation, in which the pullbackoperation spans only a portion of the total anatomical region to beimaged. Image analysis step 305 may be performed in real time toidentify regions of interest “on the fly”. Such regions of interest maythen be displayed to a user for real-time selection and subsequentautomation of the second pullback, displacement and imaging operationsin steps 320-300, for example, in a push-pull reciprocal fashion.Alternatively, the regions of interest may be automatically selected forsubsequent analysis, as described above, and steps 320-330 areautomatically performed. After having performed steps 300-330 based on apartial pullback operation, additional partial pullback operations arerepeated, as shown at 340, until the minimally invasive procedure isdeemed complete.

In one embodiment, image processing is employed to assist in identifyingthe start and stop points of a region of interest during a secondarypullback operation. In general, there may be some inaccuracy in theability to accurately determine a relative position of the imaging probefor secondary pullback operations using many of the position-sensors dueto slack in the imaging conduit, cardiac motion, flow and potentialinadvertent movement of the catheters by the user.

In one embodiment, the positioning system is used as a first estimate ofwhen to start and/or stop a secondary pullback operation, and one ormore original images taken near the start/stop points from the firstpullback operation are employed to compare against the current imagesacquired during the second pullback operation until an adequate match isfound and the beginning of a region of interest is accuratelyidentified. In addition to pathological regions of interest, suchrelative positioning may be improved using normal anatomical landmarks,such as bifurcations of the vascular anatomy.

Image comparison for determining the accurate starting position of aregion of interest during a secondary imaging operation may be achievedby one of several known image comparison methods. In one embodiment,image cross-correlation is employed. In another embodiment, the size ofthe vessel lumen is employed. In yet another embodiment, the shape ofthe vessel border (between the media and adventitia layers) is employed.In yet another embodiment, the shape of the lumen border is employed. Inyet another embodiment, the presence, shape or size of one more featuresdetected by the first imaging modality, such as calcifications,bifurcations, implants, plaque, thrombus etc are employed. In oneembodiment, a combination of position sensor information, imagecomparison techniques and/or geometric features of the regions areemployed to help identify the start and/or stop points.

In one embodiment, the real-time processing of images is performed tosupport real-time displacement and imaging by the second imagingmodality without requiring a second pullback operation. This real-timeembodiment is illustrated in the flow chart provided in FIG. 7. In step400, after having positioned the imaging probe at an initial location,one or more images are obtained using the first imaging modality. Theimages are processed in step 410 according to methods described in theabove embodiments. The real-time image processing may involve processingof individual images on an isolated basis to determine whether or not animage corresponding to the current location of the imaging probe is ofinterest for secondary imaging, or determining whether or not thecurrent position corresponds to a region of interest based on anaggregated analysis of images in a spatial region preceding the presentposition. Alternatively, the real-time image processing may involveprocessing of a sequence of images that would correspond to a 3D datasetto provide greater certainty as to the presence of a region of potentialinterest for imaging with the second modality.

In step 420, a decision is made as to whether or not the currentposition corresponds to a region of interest. If the results from theimage processing step suggest that the current position corresponds to aregion of interest, then step 430 is performed, and a media displacementoperation is directed. In another example, the decision may also bebased on information from a fiducial marker (such as, but not limitedto, a marker band detectable via angiography). As noted above, this maybe performed either in an automated fashion, or in a semi-automatedfashion in which the system prompts the operator to perform or activatethe medium displacement operation. After the medium displacementoperation is initiated, the secondary imaging modality is employed instep 440 to obtain images at the current position. The imaging probe isthen translated to a new position in step 450, and the process isrepeated according to step 460.

If, however, in step 420, the current position is not deemed tocorrespond to a region of interest, steps 430 and 440 are bypassed, andstep 450 is executed by translating the imaging probe to a new position.The process is then repeated according to step 460. The aforementionedreal-time method is either performed in a stop-start manner, asdisclosed, where the imaging probe is at rest when medium displacementand secondary imaging steps are performed, or with continuous pull-back.

Although the preceding embodiment was illustrated as a series ofdiscrete steps, it is to be understood that other variations of theembodiment may implemented. For example, in a variation of the aboveembodiment, the imaging probe may be translated using a motor or otherdrive system that is not immediately stopped while the image processingstep is performed, such that by the time that the determination is madethat a region of interest has been identified, the probe (or functionalcomponent of the probe) may have been translated slightly beyond theposition at which the images were obtained. In one example, this may beremedied by translating the functional component of the image probe inbackwards direction by a suitable amount prior to initiating thedisplacement operation. Alternatively, if the overshoot is sufficientlysmall, the displacement operation may be directly initiated without acorrective backward translation step. In other embodiments, the imagingprobe may be translated continuously while performing one or more ofsteps 400 to 430 of FIG. 7.

In one embodiment, where continuous pullback is employed, the controllerfor the secondary imaging modality can identify when suboptimal imagingdata has been acquired and declare (for example, via a notification)that a fault has occurred. The fault may be responded to by reversingthe direction of translation of the imaging probe until the region thatcorresponded to the fault has been traversed, and re-initiating steps430 to 450 while resuming the normal direction of translation.

Alternatively, having initiated a medium displacement operation in step430 based on identifying a particular position as a region of interest,the medium displacement operation may continue to be activated whilerepeating the process, until a new position is reached that is no longeridentified as a region of interest. When such a new position is reached,the medium displacement operation is terminated after performing step420, and before performing step 450. Such an embodiment enables theautomation of a serial measurement cycle in which secondary imaging isperformed at multiple successive positions without having to terminateand re-initiate a medium displacement operation.

In a variation of the above approach, it may be preferable to translatethe imaging probe in a reverse direction over a small distance prior toperforming a medium displacement operation. Alternatively, a smallreverse step (for example, on the order of <20 mm, and more preferably<5 mm) may be taken after automatically identifying the start of regionof interest so that the leading edge of the region of interest isincluded with the imaging data collected after blood is displaced. Forexample, a pullback operation may be executed until a region of interestis identified, upon which a reverse (e.g. push-forward) step ofapproximately 2 mm is taken, followed by the initiation of a mediumdisplacement operation. The pullback operation is then, resumed forimaging with the secondary (and optionally the primary) imagingmodalities, until end of a region of interest is identified, at whichpoint the displacement operation is ceased. This method would then berepeated to identify and image the next region of interest.

An imaging probe for use with the aforementioned real-time embodimentsmay include a more proximal sensor for detection of regions of interestbased on the first imaging modality (compatible with the intraluminalmedium) and a more distal sensor based on a second imaging modalitywhose performance is improved via detection of regions of interest bythe more proximal sensor and the displacement of the intraluminalmedium.

More generally, an imaging probe for use with the aforementionedreal-time embodiments may include a sensor positioned or oriented on theprobe for detection of regions of interest based on the first imagingmodality (compatible with the intraluminal medium) such that it willassess a potential region of interest before a second sensor based on asecond imaging modality is positioned or oriented to assess thecorresponding regions of interest, whose performance is improved viadetection of regions of interest by the first sensor and thedisplacement of the intraluminal medium.

While some of the aforementioned embodiments employ a second pullbackoperation to obtain images using the second imaging modality incombination with a displacement operation, it is to be understood thatthe second imaging step may be executed by directing the probe in aforward direction as opposed to a reverse direction. In particular, sucha push-forward operation may be favorable as the imaging assembly willbe moving in the same direction as a bolus of displacing fluid, allowingmore of a vessel to be imaged with a given amount of displacement fluid(because the imaging core follows the displacing fluid rather thantravelling in an opposite direction of it). Furthermore, it is to beunderstood that a pullback operation may be achieved by pullback of thetotal imaging probe, or pullback of a core component of an imagingprobe.

In another embodiment, the images obtained from the first and secondimaging modalities may be processed to provide a score or indexindicating how successfully a minimally invasive procedure involvingcombined imaging modalities was executed. For example, the score orindex may be determined by calculating the percentage or absolute valueof the pullback length where adequate displacement of intraluminal mediatook place. Such a score or index could be used to determine whichdatasets provide adequate quality for the purposes of a particular studyor trial. Alternatively, the score or index could provide an indicationas to whether or not a minimally invasive procedure should be repeated,possibly with varied parameters such as sensitivity and/or speed.

It is to be understood that while the aforementioned embodiments haverecited methods and systems pertaining to multimodal imaging probescomprising two imaging modalities, the imaging probe may includeadditional imaging modalities. In one embodiment, multiple imagingmodalities compatible with the presence of an intraluminal medium may beutilized for the identification of regions of interest. Additionally,multiple imaging modalities that benefit from the displacement of thedisplaceable intraluminal medium may be employed for the imaging ofidentified regions of interest.

In the preceding embodiments, emphasis has been placed on operationswhere the region or field of view assessed by one or more sensors isdetermined substantially by translation operations, such as pullback orpush-forward operations. The methods and devices described apply equallyto other imaging systems where the region imaged, assessed or treated bythe first and second modalities is determined by operations other than atranslation. For example, the imaging probe 31 described in FIGS. 4a to4d is capable of imaging a broad region with both optical and ultrasoundimaging and the imaging angle is determined in part by the tilt angle ofdeflectable component 70. For such a probe, the embodiments forcontrolling media displacement described above and in FIGS. 6 and 7 canhave the translation operation substituted by a deflection operation.For example, when the imaging angle is large, ultrasound imaging maydetermine that there is no region of interest in the present field ofview that requires further analysis with a second imaging modality. Aregion of interest may be identified at a more forward-looking imagingangle that would benefit from media displacement operations.

Similarly, electronic steering methods, such as those used with 2D or 3Dultrasound probes, such as linear array ultrasound transducers or phasedarray transducers, do not rely solely on translation or deflection todetermine the region imaged. Such arrays may be incorporated intominimally invasive imaging probes and may be used as either the first orsecond or both of the imaging modalities for the present disclosure, andmay benefit from the use of media displacement operations.

In yet another embodiment, an external imaging apparatus may form acomponent of the system. Examples of external imaging modalities includeangiography, CT angiography, magnetic resonance imaging and externallyapplied ultrasound. In one example embodiment, shown in FIG. 8, system500 may include a fluoroscopy imaging apparatus 510 that is optionallyconnected to computing system 220 (for example, connected to processingunit 205). While performing a translation operation and collectingimages via the first or second imaging modalities, an image acquisitiontrigger signal may be provided to the external imaging apparatus thattriggers the external system to collect one or more frames of imagesduring one or more translation operations of the imaging probe. In oneexample, the signal may be provided at intervals of interest, where suchintervals may be, for example, uniformly separated in time or along therange of a translation operation. Alternatively, the intervals may occurat time intervals related to the initiation or termination of mediumdisplacement operation or at points when the imaging probe is imaging adetermined region of interest.

In another embodiment, the external imaging apparatus may be employed toidentify one or more a regions of interest. The regions of interest maythen be employed for subsequent imaging using an imaging modality of theimaging probe, wherein the imaging modality of the imaging probebenefits from the displacement of an intraluminal medium. In one exampleimplementation, the first imaging modality is a fluoroscopy imagingdevice and the system is configured for the delivery of a contrastmedium (for example, during an cardiac angiography procedure). During aninitial operation, the fluoroscopy imaging device is employed to image aregion including a lumen into which the imaging probe may be advanced.

In the case of fluoroscopy imaging, the imaging probe, or an additionalflush catheter, may be initially employed to deliver contrast mediawithin the lumen while acquiring one or more initial fluoroscopy images.The acquired initial fluoroscopy image or images may be employed toidentify one or more regions of interest to be imaged by the imagingmodality of the imaging probe. The one or more regions of interest maybe manually identified by observation of the one or more initial images.For example, one or more of the regions of interest may correspond tolocations of luminal narrowing.

In one example implementation, the external diagnostic apparatus may beemployed to guide the imaging catheter to the region of interestidentified on the one or more initial images. For example, the imagingprobe may include a fiducial marker, such as a radiopaque marker (e.g. aradiopaque marker band), which enables the identification of thelocation of the imaging assembly using the external imaging apparatus.Accordingly, the imaging probe may be positioned such that it can betranslated through a path that is known to contain one or more regionsof interest using the external imaging apparatus, and the location ofthe imaging probe during a translation operation may be tracked usingthe external diagnostic apparatus and compared to the initial images toidentify whether or not medium displacement is required at the currentlocation.

In yet another example implementation involving an external diagnosticimaging device, the imaging probe may include first and second imagingmodalities, where the first imaging modality is compatible with thepresence of an intraluminal medium, and where the second imagingmodality benefits from the displacement of the intraluminal medium. Theregions of interest for acquiring images with the second imagingmodality (while performing a medium displacement operation) may beidentified by both the external diagnostic device (as described above)and the first imaging modality (during an initial translation andimaging operation involving the first imaging modality).

Generally speaking, it is to be understood that the intraluminal mediummay be any medium that potentially impairs the performance of an imagingmodality. Furthermore, while the above embodiments relate tointraluminal probe-based imaging methods involving the displacement ofan intraluminal fluid, it is to be understood that the aforementionedmethods may be applied to any medical imaging application in which afirst imaging modality may be employed to direct the displacement of adisplaceable medium for improving or supporting imaging based on asecond imaging modality.

Suitable applications for the aforementioned embodiment of thedisclosure involve imaging of the gastrointestinal system, thecardiovascular system (including coronary, peripheral and neurologicalvasculature), respiratory system, eyes (including the retina), auditorysystem, genitourinary systems, and many others.

Finally, it is to be understood that while the preceding embodimentshave disclosed methods in which the process of obtaining images from asecond imaging modality is aided by the medium displacement operation,it is to be understood that the use of a second imaging modality is butone example of a second minimally invasive procedure that is aided orimproved by the medium displacement operation. Accordingly, on otherembodiments, the aforementioned methods may be adapted to enable aminimally invasive procedure such as automated or semi-automateddelivery of a therapy to a region of interest, where the therapyrequires or benefits from a medium displacement operation. For example,in the aforementioned methods, the secondary imaging step may becombined with, or alternatively replaced by, a treatment operation thatis performed over a region of interest while performing a mediumdisplacement operation. Non-limiting examples of such therapeuticminimally invasive procedures include photodynamic therapy, laserablation, and the application of electrical energy, such asradiofrequency energy, where the delivery of the treatment is guided bythe regions of interest identified during a pullback operation involvinga primary imaging modality that is compatible with the presence of theintraluminal medium.

The specific embodiments described above have been shown by way ofexample, and it should be understood that these embodiments may besusceptible to various modifications and alternative forms. It should befurther understood that the claims are not intended to be limited to theparticular forms disclosed, but rather to cover all modifications,equivalents, and alternatives falling within the spirit and scope ofthis disclosure.

Therefore what is claimed is:
 1. A method of directing a mediumdisplacement operation for performing a medical procedure, the methodcomprising the steps of: obtaining a first set of images from a firstimaging modality when a first translation operation of a functionalcomponent of an imaging probe is performed; spatially correlating thefirst set of images with an associated position of the functionalcomponent of the imaging probe, wherein the first imaging modality iscompatible with a presence of a displaceable medium; processing thefirst set of images and identifying a region of interest; and directinga medium displacement operation while a second translation operation ofthe functional component of the imaging probe is performed over theregion of interest; wherein the medical procedure is performed withinthe region of interest during the medium displacement operation.
 2. Themethod according to claim 1 wherein the imaging probe comprises anadditional imaging modality compatible with a presence of thedisplaceable medium, the method further comprising the steps of:obtaining an additional set of images from the additional imagingmodality when the first translation operation is performed, and whereinthe additional set of images are spatially correlated with the positionof the functional component of the imaging probe; and processing theadditional set of images and further identifying the region of interest.3. The method according to claim 1 further comprising the steps of:processing the first set of images and identifying an additional regionof interest; directing an additional medium displacement operation whilean additional translation operation is performed over the additionalregion of interest; and wherein an additional medical procedure isperformed within the additional region of interest during the additionalmedium displacement operation.
 4. The method according to claim 1wherein the first imaging modality is selected from the group consistingof grayscale IVUS, radio-frequency IVUS, Virtual Histology™, integratedbackscatter, iMap™ elastography, NIR spectroscopy, sono-luminescentimaging, microbubble enhanced IVUS, targeted microbubble enhanced IVUS,photo-acoustic imaging, fluorescence spectroscopy, biosensors, andion-selective field effect transistors.
 5. The method according to claim1 wherein the medical procedure includes the steps of obtaining a secondset of images obtained from a second imaging modality while the mediumdisplacement operation is performed, and spatially correlating thesecond set of images with an associated position of the functionalcomponent of the imaging probe.
 6. The method according to claim 5further comprising processing the first set of images and the second setof images to spatially correlate the first set of images with the secondset of images.
 7. The method according to claim 5 wherein the secondimaging modality is selected from the group consisting of OCT,angiography, angioscopy, NIR spectroscopy, Raman spectroscopy, IVUS,radio-frequency IVUS, elastography, sono-luminescent imaging,microbubble enhanced IVUS, targeted microbubble enhanced IVUS,fluorescence spectroscopy, and photo-acoustic imaging.
 8. The methodaccording to claim 1 wherein the medium displacement operation comprisesthe step of providing a flushing solution including a contrast medium,wherein the method further comprises the step of determining an adequacyof the medium displacement operation using an external imaging modality.9. A method of directing a medium displacement operation for performinga medical procedure, the method comprising the steps of: a) obtainingone or more images from a first imaging modality of an imaging probe,wherein the first imaging modality is compatible with a presence ofblood; b) processing the one or more images to identify a region ofinterest; and c) if a region of interest is identified, directing amedium displacement operation and performing a medical procedure withinthe region of interest while the medium displacement operation isperformed.
 10. The method according to claim 9 further comprising thesteps of: d) translating a functional component of the imaging probe toa new position, and e) repeating steps a) through c).
 11. The methodaccording to claim 9 wherein a functional component of the imaging probeis translated while performing any one or more of steps a), b) and c).12. The method according to claim 9 wherein the medical procedureincludes obtaining one or more images from a second imaging modality.13. The method according to claim 12 further comprising the step ofprocessing the one or more images obtained from the first imagingmodality and one or more images obtained from the second imagingmodality to spatially correlate one or more images obtained from thefirst imaging modality with the one or more images obtained from thesecond imaging modality.
 14. The method according to claim 12 furthercomprising the step of processing the one or more images obtained fromthe second imaging modality in real-time to determine a measure of aquality of the one or more images obtained from the second imagingmodality.
 15. The method according to claim 14 further comprising thesteps of: identifying when suboptimal imaging data has been acquiredusing the second imaging modality and providing a notification that afault has occurred; and obtaining an additional set of images using thesecond imaging modality.
 16. The method according to claim 9 furthercomprising the step of providing an image acquisition triggering signalto an external imaging apparatus during one or more of the firsttranslation operation and the second translation operation forcorrelating acquisition of images obtained by the external imagingapparatus with the relative position of the imaging probe.
 17. A methodof directing a medium displacement operation for performing a medicalprocedure with a probe, the method comprising the steps of: obtaining,with an external imaging apparatus, one or more images of a regionwithin which the medical procedure is to be performed; identifying aregion of interest within the one or more images; translating afunctional component of the probe to the region of interest whileobtaining one or more additional images with the external imagingapparatus; and directing a medium displacement operation whileperforming a translation operation associated with the functionalcomponent of the probe within the region of interest.
 18. A method ofdirecting a medium displacement operation for performing a medicalprocedure, the method comprising the steps of: obtaining a set ofmeasurements from a non-imaging detection modality when a firsttranslation operation of a functional component of a probe is performed;spatially correlating the set of measurements with an associatedposition of the functional component of the probe, wherein thenon-imaging detection modality is compatible with a presence of adisplaceable medium; processing the set of measurements and identifyinga region of interest; and directing a medium displacement operationwhile a second translation operation of the functional component of theprobe is performed over the region of interest; wherein the medicalprocedure is performed within the region of interest during the mediumdisplacement operation.
 19. A method of directing a medium displacementoperation for performing a medical imaging procedure, the methodcomprising the steps of: a) obtaining one or more measurements from anon-imaging detection modality of a probe, wherein the non-imagingdetection modality is compatible with a presence of a displaceablemedium; b) processing the one or more measurements to identify a regionof interest; and c) if a region of interest is identified, directing amedium displacement operation and performing a medical procedure whilethe medium displacement operation is performed.
 20. A method ofdirecting a medium displacement operation for performing a medicalprocedure, the method comprising the steps of: employing an imagingprobe to obtain a set of images using a first imaging modality in theabsence of a first translation operation, wherein the first imagingmodality imaging probe is compatible with a presence of blood;processing the set of images and identifying a region of interest;directing a medium displacement operation to displace the blood; andperforming a medical procedure within the region of interest during themedium displacement operation.
 21. The method according to claim 20wherein the imaging probe employs a scanning mechanism for varying animaging angle when collecting the set of images.
 22. The methodaccording to claim 21 wherein the imaging probe is configured forimaging in a forward-looking direction, and where the set of images areobtained in the forward-looking direction.
 23. The method according toclaim 20 wherein the imaging probe comprises an array of ultrasoundtransducers and wherein the set of images are obtained using electronicbeam steering.